Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB- and VEGF/Flt-1 signaling pathways

Alzheimer's disease (AD) is a neurodegenerative disease with elusive pathogenesis, which accounts for most cases of dementia in the aged population. It has been reported that persistent inflammatory responses and excessive chemotaxis of microglia stimulated by beta-amyloid (AD) oligomers in the brain may accelerate the progression of AD. The present study was conducted to explore whether paeoniflorin (PF), a water-soluble monoterpene glycoside isolated from the root of Paeonia lactiflora Pallas, could attenuate A beta(1-42)-induced toxic effects on primary and BV-2 microglial cells in vitro. Our data showed that PF pretreatment inhibited A beta(1-42)-induced production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 in rodent microglia. Also, the nuclear translocation of nuclear factor kappa B (NP-kappa B) subunit p65 and the phosphorylation of NF-kappa B inhibitor alpha (I kappa B alpha) in A beta(1-42)-stimulated microglial cells were suppressed by PP administration. Moreover, PF treatment reduced the release of chemokine (C-X-C motif) ligand 1 (CXCL1) and chemokine (C-C motif) ligand 2 (CCL-2) from A beta(1-42)-stimulated microglia. Additionally, application of PP inhibited the increases in vascular endothelial growth factor (VEGF) and VEGF receptor 1 (Flt-1) triggered by A beta(1-42), and resulted in a concomitant reduction in microglial chemotaxis. Restoration of VEGF was noted to counteract the inhibitory effect of PF, suggesting that PP mitigated A beta(1-42)-elicited microglial migration at least partly by suppressing the VEGF/Flt-1 axis. In summary, in presence of A beta(1-42), PF pretreatment inhibited the excessive microglial activation and chemotaxis. (C) 2015 Elsevier B.V. All rights reserved.